DESCRIPTION Some of the clinical complications of diseases such as cystic fibrosis (CF) that are characterized by chronic lung infections are associated with increased stiffness of the sputum lining the lung epithelium. The parent project on which this FIRCA is based involves documentation of actin filaments and DNA fibers in the extracellular space of CF sputum, analysis of their contributions to the abnormal viscoelasticity of these sputa, and evaluation of the effects of potential mucolytic agents that disrupt actin filaments. The proposed collaboration will apply immuno-detection techniques to identify additional cytoskeletal elements in CF sputum (other than actin/DNA) that contribute to the viscoelasticity of CF sputum. Another aspect of the collaboration will be to analyze a series of well controlled sputum samples from Estonian patients not yet treated with DNase-based mucolytics. Such analyses will provide necessary controls for the pre-clinical therapeutic evaluation of mucolytic agents. Blood plasma and other extracellular fluids will be analyzed for circulating levels of the actin scavenger system and for cytoskeletal antibodies in patients with CF or other diseases where chronic inflammation or cell destruction is prevalent. Such analyses will evaluate the extent to which the body's normal scavenger systems regulate actin and DNA levels in body fluids and will also test the hypothesis that some of the damage in chronic inflammatory diseases results from auto-immune reactions occurring either as part of the disease or as a consequence of therapies that release these cytoskeletal materials to the circulation. An extension of this hypothesis forms the basis for a search for extracellular cytoskeletal materials in clinical samples obtained from a variety of other inflammatory gastrointestinal diseases that are a special interest of the foreign laboratory.